TY - JOUR
T1 - Rescue of a telomere length defect of Nijmegen breakage syndrome cells requires NBS and telomerase catalytic subunit
AU - Ranganathan, Velvizhi
AU - Heine, Walter F.
AU - Ciccone, David N.
AU - Rudolph, Karl L.
AU - Wu, Xiaohua
AU - Chang, Sandy
AU - Hai, Hua
AU - Ahearn, Ian M.
AU - Livingston, David M.
AU - Resnick, Igor
AU - Rosen, Fred
AU - Seemanova, Eva
AU - Jarolim, Petr
AU - DePinho, Ronald A.
AU - Weaver, David T.
N1 - Funding Information:
We are grateful to Dr. Pat Concannon for contributing NBS cell lines. This work was supported by National Institutes of Health grants CA54326 and CA79658 to D.T.W. We thank members of the Weaver, DePinho, and Livingston labs for helpful comments.
PY - 2001/6/26
Y1 - 2001/6/26
N2 - Nijmegen breakage syndrome (NBS) is a rare human disease displaying chromosome instability, radiosensitivity, cancer predisposition, immunodeficiency, and other defects [1, 2]. NBS is complexed with MRE11 and RAD50 in a DNA repair complex [3-5] and is localized to telomere ends in association with TRF proteins [6, 7]. We show that blood cells from NBS patients have shortened telomere DNA ends. Likewise, cultured NBS fibroblasts that exhibit a premature growth cessation were observed with correspondingly shortened telomeres. Introduction of the catalytic subunit of telomerase, TERT, was alone sufficient to increase the proliferative capacity of NBS fibroblasts. However, NBS, but not TERT, restores the capacity of NBS cells to survive γ irradiation damage. Strikingly, NBS promotes telomere elongation in conjunction with TERT in NBS fibroblasts. These results suggest that NBS is a required accessory protein for telomere extension. Since NBS patients have shortened telomeres, these defects may contribute to the chromosome instability and disease associated with NBS patients.
AB - Nijmegen breakage syndrome (NBS) is a rare human disease displaying chromosome instability, radiosensitivity, cancer predisposition, immunodeficiency, and other defects [1, 2]. NBS is complexed with MRE11 and RAD50 in a DNA repair complex [3-5] and is localized to telomere ends in association with TRF proteins [6, 7]. We show that blood cells from NBS patients have shortened telomere DNA ends. Likewise, cultured NBS fibroblasts that exhibit a premature growth cessation were observed with correspondingly shortened telomeres. Introduction of the catalytic subunit of telomerase, TERT, was alone sufficient to increase the proliferative capacity of NBS fibroblasts. However, NBS, but not TERT, restores the capacity of NBS cells to survive γ irradiation damage. Strikingly, NBS promotes telomere elongation in conjunction with TERT in NBS fibroblasts. These results suggest that NBS is a required accessory protein for telomere extension. Since NBS patients have shortened telomeres, these defects may contribute to the chromosome instability and disease associated with NBS patients.
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U2 - 10.1016/S0960-9822(01)00267-6
DO - 10.1016/S0960-9822(01)00267-6
M3 - Article
C2 - 11448772
AN - SCOPUS:0035954284
SN - 0960-9822
VL - 11
SP - 962
EP - 966
JO - Current Biology
JF - Current Biology
IS - 12
ER -